Investigation of the Effect of Some Optically Active Imine Compounds on the Enzyme Activities of hCA-I and hCA-II under In Vitro Conditions: An Experimental and Theoretical Study

J Biochem Mol Toxicol. 2016 Jun;30(6):277-86. doi: 10.1002/jbt.21788. Epub 2016 Jan 13.

Abstract

Inhibitors of carbonic anhydrase (hCA; EC 4.2.1.1) are used as medicines for many diseases. Therefore, they are very important. In this study, a known series of Schiff bases were synthesized and their effects on the activities of hCA-I and hCA-II, which are cytosolic isoenzymes of carbonic anhydrase, were investigated under in vitro conditions. The synthesized compounds (H1, H2, H3, and H4) were found to cause inhibition on enzyme activities of hCA-1 and hCA-II. IC50 values of H1, H2, H3, and H4 compounds were 140, 88, 201, and 271 μM for hCA-I enzyme activity and 134, 251, 79, and 604 μM for hCA-II enzyme activity, respectively. The synthesized Schiff bases were characterized by several methods, including (1) H NMR, FT-IR, elemental analysis, and polarimetric measurements. Correlation coefficient square values (R(2) ) of comparison of the theoretical and experimental (1) H NMR shifts for H1, H2, H3, and H4 compounds were found as 0.9781, 0.9814, 0.9758, and 0.8635, respectively.

Keywords: Carbonic Anhydrase; Chirality; DFT; Inhibition; Theoretical NMR.

MeSH terms

  • Carbonic Anhydrase I / antagonists & inhibitors*
  • Carbonic Anhydrase I / chemistry
  • Carbonic Anhydrase I / isolation & purification
  • Carbonic Anhydrase II / antagonists & inhibitors*
  • Carbonic Anhydrase II / chemistry
  • Carbonic Anhydrase II / isolation & purification
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Enzyme Assays
  • Erythrocytes / chemistry
  • Erythrocytes / enzymology
  • Humans
  • Imines / chemical synthesis
  • Imines / chemistry*
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Schiff Bases / chemical synthesis
  • Schiff Bases / chemistry*
  • Spectroscopy, Fourier Transform Infrared
  • Structure-Activity Relationship

Substances

  • Carbonic Anhydrase Inhibitors
  • Imines
  • Schiff Bases
  • Carbonic Anhydrase I
  • Carbonic Anhydrase II